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PURPOSE: The aim of this study is to describe the variable phenotype of congenital corneal opacities occurring in patients with biallelic CYP1B1 pathogenic variants. METHODS: A retrospective chart review was conducted to identify patients with congenital corneal opacities and CYP1B1 pathogenic variants seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, anterior segment optical coherence tomography, histopathologic images, and details of genetic testing were reviewed. RESULTS: Three children were identified. All presented with raised intraocular pressure. Two patients showed bilateral limbus-to-limbus avascular corneal opacification that did not resolve with intraocular pressure control; 1 showed unilateral avascular corneal opacity with a crescent of clear cornea, iridocorneal adhesions, iridolenticular adhesions, and classical features of congenital glaucoma in the fellow eye (enlarged corneal diameter, Haab striae, and clearing of the corneal clouding with appropriate intraocular pressure control). The first 2 patients were visually rehabilitated with penetrating keratoplasty. Histopathology revealed distinct features: a variably keratinized epithelium; a thick but discontinuous Bowman-like layer with areas of disruption and abnormal cellularity; Descemet membrane, when observed, showed reduced endothelial cells; and no pathological changes of Haab striae were identified. Two patients had compound heterozygous pathogenic variants in CYP1B1 causing premature stop codons, whereas 1 was homozygous for a pathogenic missense variant. CONCLUSIONS: Congenital corneal opacities seen in biallelic CYP1B1 pathogenic variants have a variable phenotype. One is that commonly termed as Peters anomaly type 1 (with iridocorneal adhesions, with or without iridolenticular adhesions) and the other is a limbus-to-limbus opacity, termed CYP1B1 cytopathy. Clinicians should be aware of this phenotypic variability.

Assuntos

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PURPOSE: The aim of this study was to report a case of corneal plana-like phenotype with bilateral peripheral scleralization associated with a PITX2 pathogenic variant. METHODS: Clinical findings were obtained by ophthalmologic examination. Molecular diagnosis was performed by whole-exome sequencing in the patient and his parents. RESULTS: A 12-month-old male patient present with bilateral peripheral corneal scleralization, corneal plana-like phenotype, and iris hypoplasia. The genetic analysis revealed a de novo PITX2 pathogenic variant (c.323G>A, p.R108H). CONCLUSIONS: PITX2 c.323G>A (p.R108H) can be associated with a unique corneal plana-like phenotype with peripheral scleralization, and thus, PITX2 should be targeted in genetic testing of this specific phenotype.

Assuntos

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PURPOSE: The purpose of this study was to describe the deep phenotype of congenital corneal opacities (CCO) in patients with 22q11.2 deletion syndrome (22q11.2 DS) and to identify putative regions or genes that could explain the CCO. METHODS: A retrospective chart review was conducted to identify patients with 22q11.2 DS seen in the ophthalmology clinic of a tertiary referral children's hospital. Thirty patients were identified, with molecular confirmation. Twenty-six did not show structural anterior segment anomalies aside from posterior embryotoxon (n = 4), whereas 4 had bilateral CCO, of which 3 had preoperative images. We reviewed medical, operative, and pathology reports; anterior segment optical coherence tomography; high-frequency ultrasound; histopathologic slides; and genetic testing. To identify putative genes responsible for CCO, chromosomal breakpoints in patients with and without CCO were compared. RESULTS: In the 3 patients with preoperative imaging and CCO, a pattern of paracentral corneal opacification with central clearing accompanied by iridocorneal or keratolenticular adhesions was observed. Anterior segment optical coherence tomography and histopathologic images showed central stromal thinning with a residual structure consistent with Descemet membrane. One patient presented at birth with unilateral corneal perforation, suggestive of likely stromal thinning. A comparison of the breakpoints across all cases failed to reveal unique regions or genes in patients with CCO. CONCLUSIONS: 22q11.2 DS can rarely be associated with CCO. We describe a consistent pattern of central clearing related to posterior stromal thinning, with or without ICA/KLA. Possible candidate genes for corneal opacification in 22q11.2 DS remain elusive.

Assuntos

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Reports of systemic associations in patients with Isolated Sagittal Synostosis (ISS) are sparse. Craniofacial surgeons, and other providers, should be aware that a significant proportion of patients with ISS may have syndromic or systemic involvement. This study investigates the incidence of systemic disease and syndromic diagnosis in a cohort of patients presenting with ISS (ie, patients with sagittal synostosis without other sutural involvement). METHODS: This study consists of a retrospective review of patients diagnosed with ISS between 2007 and 2017 at a single institution. Patients were divided according to onset (early <1 year, late >1 year) of ISS. Patient notes were examined for congenital anomalies, systemic conditions, and molecular testing. Only patients with isolated sagittal fusion-meaning, patients with sagittal synostosis and no other sutural involvement-were included. RESULTS: Three hundred seventy-seven patients met the inclusion criteria: systemic conditions were identified in 188/377 (50%) of them. One hundred sixty-one patients with early onset (Group A), and 216 patients with late onset ISS (Group B) were identified. Systemic involvement was identified in 38% of Group A and 60% of Group B, which was statistically significant (P < 0.001). Forty-eight of 377 (13%) of patients had a syndromic diagnosis, and 79% of these were confirmed via genetic testing. Thirty-five percent of patients were diagnosed with central nervous system anomalies and 16% had craniofacial anomalies. CONCLUSIONS: Nearly 50% of the patients initially diagnosed with ISS were found to have some form of systemic involvement. This supports affording full pediatric and genetic evaluation with molecular testing to these children.

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PURPOSE: Corneal involvement in mitochondrial disease is seldom described. Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by retinitis pigmentosa, external ophthalmoplegia, and heart block. We report 2 patients with KSS with corneal lesions involving the endothelium, which improved with Coenzyme Q10 (CoQ10). Based on recent research regarding the role of dysfunctional oxidative metabolism in Fuchs Endothelial Corneal Dystrophy (FECD), we propose that mitochondrial diseases and FECD share a final pathway. METHODS: A chart review was performed and a review of the literature was completed with a PubMed search using the terms "Kearns-Sayre Syndrome", "mitochondria", "endothelium", "Fuchs endothelial corneal dystrophy", and "cornea". RESULTS: There are 19 reports of corneal involvement in clinical phenotypes of mitochondrial disease. Nine of these 19 cases had findings consistent with KSS. Our patients with KSS had microcystic changes throughout the cornea and excrescences on the endothelial surface seen with ultrasound biomicroscopy, similar to the clinical findings in FECD. CoQ10 improved corneal disease in both children. CoQ10 deficiency has been reported in a variety of mitochondrial diseases, and efficacy of supplementation has been demonstrated. It may be beneficial in these patients because of its antioxidant properties and role in oxidative phosphorylation. CONCLUSIONS: The common deletion found in patients with KSS has recently been implicated in FECD, which has recently been shown to be a disease related to dysfunctional oxidative metabolism. Future research should explore the use of antioxidants, such as CoQ10 in patients with FECD.

Assuntos

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Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that shows greater severity in females and is largely attributed to mutations in EFNB1. A 7-year-old boy presented with hypertelorism, broad nasal root, midfacial hypoplasia, mandibular prognathia, ptosis, and scaphocephaly was clinically diagnosed with CFNS. Three-dimensional computed tomographic scans confirmed the isolated sagittal synostosis. His mother also showed clinical features of CFNS, but less severe. Genetic tests uncovered a novel C to T mutation at nucleotide 466 (c.466C>T) in exon 1 of EFNB1 for both. To the best of our knowledge, this is the only reported incident of CFNS in a male child exhibiting isolated sagittal synostosis.